Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA.
Osteoarthritis Cartilage. 2010 May;18(5):629-39. doi: 10.1016/j.joca.2009.12.013. Epub 2010 Feb 16.
To evaluate the efficacy and safety of the cyclooxygenase-inhibiting nitric-oxide donator, naproxcinod, compared with naproxen and placebo in patients with osteoarthritis (OA) of the knee.
918 eligible patients were randomly assigned to double-blind treatment with either naproxcinod 375 mg, naproxcinod 750 mg, naproxen 500 mg or placebo, twice daily for 13 weeks. The primary objective was to show superiority of naproxcinod compared to placebo. Main efficacy criteria were assessment of pain and physical function using the Western Ontario and MacMaster Universities Osteoarthritis Index (WOMAC) and patients' overall rating of disease status (Likert scale). The main secondary objectives were to show that naproxcinod was non-inferior to naproxen 500 mg and to evaluate overall safety.
Both doses of naproxcinod were statistically and clinically superior to placebo in relieving signs and symptoms of OA of the knee after 13 weeks of treatment, as demonstrated by all three co-primary endpoints (P< or =0.0003). The evaluation of the other secondary efficacy measures was consistent with the primary endpoint results. Naproxcinod 750 mg was non-inferior to equimolar doses of naproxen 500 mg in the Intent-to-Treat (ITT) population. 24.5% of patients discontinued prematurely, with a higher incidence in the placebo group (18.6%) than the active groups (4.3-7.1%) discontinuing due to lack of efficacy. Both doses of naproxcinod were well-tolerated, with most adverse events being mild or moderate. Compared to placebo, naproxcinod 750 mg and 375 mg showed a similar blood pressure (BP) profile in contrast to naproxen which increased BP.
These results demonstrated the clinical efficacy and safety of naproxcinod in the management of the signs and symptoms of OA. Naproxcinod was well-tolerated, with BP effects similar to placebo and different from naproxen. Clinical Trials.gov identifier: NCT00542555.
评估环氧化酶抑制一氧化氮供体萘普生昔定（naproxcinod）在膝骨关节炎（OA）患者中的疗效和安全性，与萘普生和安慰剂进行比较。
918 名符合条件的患者被随机分配至双盲治疗，分别接受萘普生昔定 375mg、750mg、萘普生 500mg 或安慰剂，每日 2 次，治疗 13 周。主要目标是证明萘普生昔定优于安慰剂。主要疗效标准是使用西部安大略省和麦克马斯特大学骨关节炎指数（WOMAC）评估疼痛和身体功能，以及患者对疾病状况的整体评价（Likert 量表）。主要次要目标是证明萘普生昔定与萘普生 500mg 等效且评估整体安全性。
在 13 周的治疗后，两种剂量的萘普生昔定在缓解膝骨关节炎的体征和症状方面均优于安慰剂，所有三个主要终点（P<或=0.0003）均具有统计学和临床意义。对其他次要疗效指标的评估与主要终点结果一致。萘普生昔定 750mg 在在意向治疗（ITT）人群中与等摩尔剂量的萘普生 500mg 等效。24.5%的患者提前停药，安慰剂组（18.6%）的发生率高于活性药物组（4.3-7.1%），因疗效不佳而停药。两种剂量的萘普生昔定都具有良好的耐受性，大多数不良事件为轻度或中度。与安慰剂相比，萘普生昔定 750mg 和 375mg 显示出与萘普生相似的血压（BP）谱，而萘普生则升高 BP。
这些结果表明萘普生昔定在治疗 OA 体征和症状方面具有临床疗效和安全性。萘普生昔定具有良好的耐受性，BP 效应与安慰剂相似，与萘普生不同。临床试验.gov 标识符：NCT00542555。
